Opinion | H5N1’s Growing Threat: Risks to Humans and Wildlife Are Increasing

In this Instagram Live discussion, MedPage Today editor-in-chief Jeremy Faust, MD, speaks with Nahid Bhadelia, MD, founding director of the Boston University Center on Emerging Infectious Diseases, about the current state of H5N1.

Faust and Bhadelia discuss the virus’s unusual behavior, the broader ecological impact of the outbreak, and why the case fatality rate may not be as high as previously feared.

Following is a partial transcript of the video (note that errors are possible):

Faust: Let’s dive in. Let me just introduce you to everybody. Nahid Bhadelia is the founding director of the Boston University Center on Emerging Infectious Diseases, CEID. And previously spent, gosh, how long in the White House at… a while.

Bhadelia: Yes, a year.

Faust: A year in the White House COVID-19 response team. And while there, working on vaccine availability donation programs, as well as some really important projects about the future of pandemics funding, which I wonder if it still exists, but that’s for another time. Welcome and thanks for coming on.

Bhadelia: Thanks for having me, Jeremy.

Faust: So H5N1, just from your perspective, where are we right now?

Bhadelia: Yeah, I think the general concern is that this is a virus that we’ve known for a long period of time, but it’s behaving in ways that we had not been expecting it to, particularly in the last 2 years. And even though thankfully, there does not seem to be any signs of human-to-human, sustained human-to-human transmission at least, we are in a situation where there’s so many animals affected around us that the chances of a human sporadically coming into contact with an animal and potentially getting infected has increased.

And that’s concerning because the more chances this virus has to adapt to humans, that potential — as you’ve called it, the Russian roulette — the Russian roulette just gets loaded over and over again for a potential chance for a further evolution of the virus to adapt to mammalian physiology, to either include severity, which we already know traditionally can, or to potentially transmit between them.

Faust: So why do you think that so far, the case fatality rate that we’ve seen is quite low? And I will back up by saying usually early in an outbreak, the opposite happens, which is we have an increased case fatality rate because we missed all the mild cases. This time we’re told, well, historically, the case fatality rate for H5N1 could be as high as 40%, which sounds crazy high. Even if it was 10 times less, 4%, we’re still nowhere near that. Why do you think that is?

Bhadelia: Yeah, good question. And it’s funny you introduced me as somebody who was like, my primary affinity is not having been part of the White House. My primary affinity is basically being a clinician who does a lot of emerging infectious diseases responses; I was part of the Ebola response. It’s part of another disease where as you said, well, what we traditionally have known about Ebola and Marburg is that mortality is pretty high, but when you actually see enough cases, all diseases have these two standard deviations.

So to your point about H5N1, with the mortality being so high, it’s possible that the traditional presentation was the sickest that presented, and that we are starting to see a different population. Traditionally, we were seeing cases in parts of Europe and parts of Asia, so demographics of the population.

So here’s some theories that are abound about why currently a majority of the cases in the U.S. have been on the milder side, not all. Partly the way that people are getting infected from this virus. So a majority of the human cases have been among cattle, cattle farm workers, and in that population, the exposure is to highly concentrated virus in the milk. So it’s more of a contact rather than respiratory exposures that traditionally are seen in the prior smaller cases, cluster of cases that have happened in Asia on bird farms, etc. So is it the route of transmission? Is it the way the virus is being introduced that it’s not primarily through the respiratory, rather through the conjunctiva or through contact?

The second thought has been, there’s actually a ferret study that showed that when ferrets were exposed to the H1N1, the 2009 H1N1, they had a much milder outcome with H5N1. Traditionally, the mortality in ferrets with H5N1 is pretty high. So is our population different immunologically because it’s been exposed to different flu strains in the past, which has built a different kind of immunity? We just don’t know. Is it the particular virus that is circulating, the B3.313? Is it the current genotype that somehow is different? Not enough about which one of these is playing the major role.

Faust: Yeah, and I’ll add to that by saying that there are two major strains that we’re following here, one of which has been responsible as far as we know for most of the cases. And then we had the Canadian case, which was this young teenager who almost died, was on lung bypass ECMO [extracorporeal membrane oxygenation], was intubated, had cytokine storm, the whole kitchen sink was thrown at this person. She survived. And that was the other strain.

And then I think the Louisiana death was, I believe, also that strain. And so the question is the main B3 strain going through the cattle and through the birds, is this just — it’s OK to say — is this just a milder thing or is it, as you said, that plus the fact that we’re seeing it in a population who we normally wouldn’t even detect? So we don’t want to say, oh, it’s mild because a lot of the cases are healthy 30-year-olds.

On the other hand, I will just say when you do the math of it, there have been something close to 70 confirmed human cases in the U.S. but with serology, these antibody studies, we know it’s got to be 10 times more than that, and maybe even more. And so by now, if it were truly, even in a young population, if you had 1,000 people with COVID in 2020, you’d see hospitalizations. And that’s not the case with this.

Bhadelia: That’s not the case. And so is it, again, it’s more exposures, the way people are getting exposed, the incident of it, the route of transmission that’s an issue. And again, it’s because who it’s finding at that interface between animals and humans, I still think some of it is the population that’s been exposed, but this young person got very sick.

And again, the only way that we can tease it out is that aside from studying the population that is contact and at the interface with humans is to keep a broader lens open, which is why I was so glad to see that one of the things that the CDC did under the Biden administration in January with their HAN [Health Alert Network] was to introduce this idea that anybody who’s sick in the ICU [intensive care unit] or admitted with an influenza A, right — which your current testing in the hospitals will pick up H5N1, but it will pick it up as an influenza A. So anybody who’s critically ill with influenza A should undergo further genotyping to look to make sure it’s not H5. And that’s a great broader net just to make sure we’re not missing anything.

Faust: And I think just to expand that just a bit, that’s the Health [Alert] Advisory Network from CDC, putting out a communication saying, look, if you have a patient who’s sick enough with flu to be in the ICU, they should actually have further testing to see if it’s seasonal flu or bird flu. And on top of that, I believe, and certainly the case here in Massachusetts, they want us to do that testing for others as well, including people who would have exposures to professional, either they’re farmers, or if they happen to, as this person in Louisiana did, just to mess around with a bird in the backyard. So don’t do that.

Bhadelia: Yeah. Well, it’s interesting, right? Aside from backyard flocks, people keep bird feeders in the backyard and there are, I think it’s in the order of 140 million deaths in birds. We’re talking about the magnitude of it. It’s putting a lot of bird, wild bird species back into extinction sort of areas like the bald eagle nest failures, and we’re losing thousands and thousands of our national bird. It’s wreaking ecological havoc we’re not aware of.

And I bring it up because all of our backyards are at risk. It’s not just the backyard flocks and clearly they’re at the highest risk. And this idea of how do we deal with dead birds in ponds, in schools, how do we deal with bird feeders and seeing sick and dead birds in our backyards? I think it is an awareness, even if the risk of the pandemic is not here, the risk of everyday potential exposures we need to raise increasing awareness about.

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